Multiple Sclerosis Center, University of Pennsylvania, 3400 Spruce St, 3 W Gates Bldg, Philadelphia, PA 19104, USA.
Am J Manag Care. 2010 Sep;16(8 Suppl):S211-8.
When introduced in the early and middle 1990s, current first-line pharmacologic therapies for multiple sclerosis (MS)--interferon beta-1a, interferon beta-1b, and glatiramer acetate--constituted a major advancement in MS treatment. Nevertheless, disease progression, although typically delayed with these agents, remains inevitable in most patients and constitutes a significant limitation of the currently available treatments. Moreover, the first-line therapies all require frequent subcutaneous or intramuscular injections, delivery modalities that are associated with subpar treatment adherence. The demand for more effective agents has produced a new generation of MS therapies with impressive efficacy profiles--although their long-term safety and tolerability remain largely unknown. Some of the new agents have been formulated for oral administration, which will likely have a positive impact on treatment adherence. These new agents are appearing during a time of major change in MS research. As the old expectation of inevitable disease progression is being reconsidered, the notion of sustained disease inactivity has become a credible, still somewhat elusive, goal. Neuroprotection may also be possible with new and existing treatments. At the same time, new imaging techniques, such as measuring disease progression via T1-hypointense lesions ("black holes"), and a better understanding of pathophysiologic factors in MS--such as the role of neurotrophic growth factors and oxidative stress--are changing the ways that efficacy is measured and how new agents are developed.
当在 20 世纪 90 年代早期和中期引入时，目前多发性硬化症（MS）的一线药物治疗——干扰素 beta-1a、干扰素 beta-1b 和醋酸格拉替雷——是 MS 治疗的重大进展。尽管这些药物通常可以延迟疾病进展，但在大多数患者中仍然不可避免，这构成了目前可用治疗方法的重大局限性。此外，一线治疗都需要频繁进行皮下或肌肉注射，而这些给药方式与较差的治疗依从性有关。对更有效药物的需求产生了新一代具有令人印象深刻疗效的 MS 治疗方法——尽管它们的长期安全性和耐受性在很大程度上仍然未知。一些新的药物已被制成口服制剂，这可能会对治疗依从性产生积极影响。这些新的药物出现在 MS 研究发生重大变化的时期。随着对不可避免的疾病进展的旧期望被重新考虑，疾病持续不活跃的概念已成为一个可信的、仍然有些难以捉摸的目标。神经保护也可能通过新的和现有的治疗方法实现。与此同时，新的成像技术，如通过 T1 低信号病变（“黑洞”）测量疾病进展，以及对 MS 中病理生理因素的更好理解，如神经营养生长因子和氧化应激的作用，正在改变疗效的测量方式以及新药物的开发方式。
